Next generation sequencing technologies (NGS) are revolutionizing the advancement of tests which are used to diagnose a patient’s risk for a specific disease state. These tests, however, are also proposing an especially difficult challenge for the FDA who is tasked with regulating NGS’s fluid processes and procedures. As a result of the surge in NGS development, the FDA has released a discussion paper on probable methods for demonstrating the analytical and clinical capabilities of NGS technologies and is requesting public comment. While multiple stakeholders including academia, government regulators and industry manufacturers all support future innovation within NGS tests, the need for clear and well developed regulatory framework is necessary in order for the industry to move forward in the development and application of these tests.